Good Cascade Impactor Practices - Good Cascade Impactor Practices, AIM and EDA for Orally Inhaled Products - page 92

Fig. 4.3 Schematic diagram showing the principle of compendial methodology for DPI testing
with CI
aerosol plume emitted from the inhaler mouthpiece [ 2 ]. This plume initially
moves faster than the sampling flow into the IP, resulting in limited time for
evaporation and for the reduction in emitted droplet sizes. It therefore follows
that deviations from nominal dimensions and associated tolerances will influ-
ence APSD measurements for any given design of IP [ 69 - 71 ].
The compendia advise that consideration should also be given to the internal
surface roughness as its magnitude may influence measurement variability (see
collection surface properties). It should be noted that although identified as part
of the CI system in one compendial monograph [ 68 ], an IP is not strictly neces-
sary for the testing of droplets emitted by nebulizing systems, including the
soft-mist plume from SMIs, because of the absence of the ballistic fraction.
(m) Vacuum pump: Different pumps may produce different time-dependent flow-
rate profiles, which are important for DPI testing [ 73 ]. In the compendial meth-
odologies for evaluating this class of OIPs, the pump-capacity-related variability
is minimized by operating the impactor with the flow set by means of a critical
orifice (Fig. 4.3 ) and by measuring the critical flow ( P 3 / P 2 < 0.5, where P 2 and P 3
are pressures upstream and downstream of the flow-control valve) [ 20 , 21 ]. P 1
is the upstream near-to-ambient pressure at the inhaler-induction port, and Q is
the volumetric flow rate through the CI system.
Because some pumps heat up and lose efficiency over time if left running,
flow-rate setting/verification and APSD measurement should be conducted as
quickly as possible, if needed.
(n) Impactor design: Bonam et al . also identified the design of a CI as another fixed
contributor to the overall method variability [ 2 ]. Detailed descriptions of the
design characteristics of each of the CI systems identified in the pharmacopeial
monographs covering aerodynamic particle size analysis have therefore been
provided as a reference source in Chap. 2 . Bonam et al . noted that although this
aspect of the test method is often fixed at the outset by the availability of equip-
ment and preference within the organization, the choice of CI may be driven by